basic Helix Loop Helix (bHLH) domain superfamily; bHLH proteins are transcriptional regulators that are found in organisms from yeast to humans. Members of the bHLH superfamily have two highly conserved and functionally distinct regions. The basic part is at the amino end of the bHLH that may bind DNA to a consensus hexanucleotide sequence known as the E box (CANNTG). Different families of bHLH proteins recognize different E-box consensus sequences. At the carboxyl-terminal end of the region is the HLH region that interacts with other proteins to form homo- and heterodimers. bHLH proteins function as a diverse set of regulatory factors because they recognize different DNA sequences and dimerize with different proteins. The bHLH proteins can be divided to cell-type specific and widely expressed proteins. The cell-type specific members of bHLH superfamily are involved in cell-fate determination and act in neurogenesis, cardiogenesis, myogenesis, and hematopoiesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASVAPVGQTLTKIETLRLTIQYISFLSSQLGLSEEEL 131
Cdd:cd18938   1 QRQSASEREKLRMRDLAKALHNLRRYLPPSVAPAGQSLTKIETLRLTIRYISHLSAQLGLSEESL 65

basic helix-loop-helix (bHLH) domain found in the mesoderm posterior protein (Mesp) family; Mesp, a bHLH tissue specific transcription factor, acts as a key regulator of the cardiovascular transcriptional network by inducing directly and/or indirectly the expression of the majority of key cardiovascular transcription factors. The Mesp family includes two bHLH transcription factors, Mesp1 and Mesp2. Mesp1, also termed Class C basic helix-loop-helix protein 5 (bHLHc5), promotes cardiovascular differentiation during embryonic development and embryonic stem cell differentiation. Mesp2, also termed Class C basic helix-loop-helix protein 6 (bHLHc6), plays an important role in somitogenesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASVAPVGQTLTKIETLRLTIQYISFLSSQLGLSEEEL 131
Cdd:cd18938   1 QRQSASEREKLRMRDLAKALHNLRRYLPPSVAPAGQSLTKIETLRLTIRYISHLSAQLGLSEESL 65

helix loop helix domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 18859021     72 SEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:smart00353   1 NARERRRRRKINEAFDELRSLLPT--LPKNKKLSKAEILRLAIEYIKSLQEEL 51

basic helix-loop-helix (bHLH) domain found in the mesoderm posterior protein (Mesp) family; Mesp, a bHLH tissue specific transcription factor, acts as a key regulator of the cardiovascular transcriptional network by inducing directly and/or indirectly the expression of the majority of key cardiovascular transcription factors. The Mesp family includes two bHLH transcription factors, Mesp1 and Mesp2. Mesp1, also termed Class C basic helix-loop-helix protein 5 (bHLHc5), promotes cardiovascular differentiation during embryonic development and embryonic stem cell differentiation. Mesp2, also termed Class C basic helix-loop-helix protein 6 (bHLHc6), plays an important role in somitogenesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASVAPVGQTLTKIETLRLTIQYISFLSSQLGLSEEEL 131
Cdd:cd18938   1 QRQSASEREKLRMRDLAKALHNLRRYLPPSVAPAGQSLTKIETLRLTIRYISHLSAQLGLSEESL 65

basic helix-loop-helix (bHLH) domain found in mesogenin-1 (Msgn1) and similar proteins; Msgn1, also termed paraxial mesoderm-specific mesogenin1, or pMesogenin1 (pMsgn1), is a bHLH transcription factor required for maturation and segmentation of paraxial mesoderm. It may regulate the expression of T-box transcription factors essential for mesoderm formation and differentiation.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18859021  60 RLKNPSERRQNASEKEKLRMRDLTKALHHLRSFLPASVAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd18939   1 KVKMSAQRRRKASEREKLRMRTLAEALHTLRNYLPPVYSQRGQPLTKIQTLKCTIQYISELSGLL 65

Helix-loop-helix DNA-binding domain;

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 18859021    67 RRQNASEKEKLRMRDLTKALHHLRSFLPASvaPVGQTLTKIETLRLTIQYISFL 120
Cdd:pfam00010   1 RREAHNERERRRRDRINDAFDELRELLPTL--PPDKKLSKAEILRLAIEYIKHL 52

basic helix-loop-helix (bHLH) domain found in neurogenin-1 (NGN-1) and similar proteins; NGN-1, also termed Class A basic helix-loop-helix protein 6 (bHLHa6), or neurogenic basic-helix-loop-helix protein, or neurogenic differentiation factor 3 (NeuroD3), is a neural-specific bHLH transcription factor involved in the initiation of neuronal differentiation. It activates transcription by binding to the E box (5'-CANNTG-3').

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18859021  58 RLRLKNPS-------ERRQNASEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLSSQLGLSEE 129
Cdd:cd19716   1 RSRVKNEAllhtikkSRRVKANDRERNRMHNLNAALDELRSVLPS--FPDDTKLTKIETLRFAHNYIWALSETLRLADQ 77

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L), pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; The family corresponds to a group of bHLH transcription factors, including FERD3L and PTF1A. FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription. PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18859021  68 RQNASEKEKLRMRDLTKALHHLRSFLPasVAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19686   2 RQAANIRERKRMRSINDAFDGLRRHIP--TFPYEKRLSKVDTLRLAIQYINFLTELL 56

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster protein taxi and similar proteins; Protein taxi, also termed protein delilah (Dei), is a bHLH transcription factor that is involved in regulation of cell adhesion and attachment that is expressed in specialized cells that provide anchoring sites to either muscles (tendon cells), or proprioceptors (chordotonal attachment cells) during embryonic development. It probably plays an important role in the differentiation of epidermal cells into the tendon cells that form the attachment sites for all muscles.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPasVAPVGQT---LTKIETLRLTIQYISFLSSQL 124
Cdd:cd11431   1 RRKTANARERDRMREINDAFEALRRAVP--EYPVAGKdgkLTKITTLRLAMNYIKALTDLL 59

basic helix-loop-helix (bHLH) domain found in neurogenin-3 (NGN-3) and similar proteins; NGN-3, also termed Class A basic helix-loop-helix protein 7 (bHLHa7), or protein atonal homolog 5 (ATOH5), is a neural-specific bHLH transcription factor expressed in the developing central nervous system and the embryonic pancreas. It is involved in neurogenesis and plays an important role in spermatogenesis.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 18859021  62 KNPSERRQNASEKEKLRMRDLTKALHHLRSFLPasVAPVGQTLTKIETLRLTIQYISFLSSQLGLSEE 129
Cdd:cd19718   3 KQKRNRRMKANDRERNRMHNLNSALDALRSVLP--TFPDDAKLTKIETLRFAHNYIWALTETLRMADH 68

basic helix-loop-helix (bHLH) domain found in scleraxis, transcription factor 15 (TCF-15) and similar proteins; The family includes scleraxis and transcription factor 15 (TCF-15). Scleraxis, also termed SCX, or Class A basic helix-loop-helix protein 41 (bHLHa41), or Class A basic helix-loop-helix protein 48 (bHLHa48), is a bHLH transcription factor that is expressed in sclerotome limb bud cranial and body wall mesenchyme, pericardium and heart valves, ligaments and tendons. It is required for tendon formation ligaments, connective tissue, the diaphragm, and testis development. Scleraxis plays a central role in promoting fibroblast proliferation and matrix synthesis during the embryonic development of tendons. TCF-15, also termed Class A basic helix-loop-helix protein 40 (bHLHa40), or paraxis, or protein bHLH-EC2, is a bHLH transcription factor expressed in caudal lateral and paraxial mesoderm dermomyotome and sclerotome fore limb buds during embryo development. It may function as an early transcriptional regulator involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18859021  68 RQNASEKEKLRMRDLTKALHHLRSFLPASvaPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd11465   1 RQAANARERDRTHSVNSAFTALRTLIPTE--PADRKLSKIETLRLASSYISHLATVL 55

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor (NeuroD) family; The NeuroD family includes NeuroD1, NeuroD2, NeuroD4 and NeuroD6. NeuroD1, also termed Class A basic helix-loop-helix protein 3 (bHLHa3), is a neuronal bHLH transcription factor involved in the development and maintenance of the endocrine pancreas and neuronal elements. It acts as an essential regulator of glutamatergic neuronal differentiation. Loss of NeuroD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice. NeuroD2, also termed Class A basic helix-loop-helix protein 1 (bHLHa1), or NeuroD-related factor (NDRF), is a neuronal calcium-dependent bHLH transcription factor that induces neuronal differentiation and promotes neuronal survival. It plays a central role in thalamocortical synaptic maturation. NeuroD2 mediates calcium-dependent transcription activation by binding to E box-containing promoter. NeuroD4, also termed Class A basic helix-loop-helix protein 4 (bHLHa4), or protein atonal homolog 3 (ATH-3), or Atoh3, or Math-3, is a bHLH transcriptional activator that mediates neuronal differentiation. NeuroD6, also termed Class A basic helix-loop-helix protein 2 (bHLHa2), or protein atonal homolog 2 (ATH-2), or Atoh2, or Math2, or Nex1, is a neurogenic bHLH transcription factor involved in neuronal development, differentiation, and survival in Alzheimer's disease (AD) brains of both cohorts. It plays an integrative role in coordinating increase in mitochondrial mass with cytoskeletal remodeling, suggesting that it may act as a co-regulator of neuronal differentiation and energy metabolism.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 18859021  68 RQNASEKEKLRMRDLTKALHHLRSFLPASVAPvgQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd11427   1 RVKANARERNRMHGLNDALDNLRKVVPCYSKT--QKLSKIETLRLARNYIWALSEIL 55

basic helix-loop-helix (bHLH) domain found in pancreas transcription factor 1 subunit alpha (PTF1A) and similar proteins; PTF1A, also termed Class A basic helix-loop-helix protein 29 (bHLHa29), or pancreas-specific transcription factor 1a, or bHLH transcription factor p48, or p48 DNA-binding subunit of transcription factor PTF1 (PTF1-p48), is a bHLH transcription factor implicated in the cell fate determination in various organs. It binds to the E-box consensus sequence 5'-CANNTG-3' and plays a role in early and late pancreas development and differentiation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLS 121
Cdd:cd11417   1 QRQAANLRERRRMQSINDAFEGLRSHIPT--LPYEKRLSKVDTLRLAIGYINFLS 53

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 1 (HEN-1) and similar proteins; HEN-1, also termed nescient helix-loop-helix 1 (Nhlh1), or Class A basic helix-loop-helix protein 35 (bHLHa35), or nescient helix loop helix 1 (NSCL-1), is a neuron-specific bHLH transcription factor that may serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18859021  52 IMRKKRRLRLKNPSERRQNASEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19701   1 LSREERRRRRRATAKYRTAHATRERIRVEAFNVAFAELRKLLPT--LPPDKKLSKIEILRLAICYISYLNHVL 71

basic helix-loop-helix (bHLH) domain found in transcription factor 15 (TCF-15) and similar proteins; TCF-15, also termed Class A basic helix-loop-helix protein 40 (bHLHa40), or paraxis, or protein bHLH-EC2, is a bHLH transcription factor expressed in caudal lateral and paraxial mesoderm dermomyotome and sclerotome fore limb buds during embryo development. It may function as an early transcriptional regulator involved in the patterning of the mesoderm and in lineage determination of cell types derived from the mesoderm.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18859021  66 ERRQNASEKEKLRMRDLTKALHHLRSFLPASvaPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd11470   7 KQRQAANARERDRTQSVNTAFTALRTLIPTE--PVDRKLSKIETLRLASSYIAHLANVL 63

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factors, Oligo2, Oligo3 and similar proteins; The family includes two bHLH transcription factors, Oligo2 and Oligo3. Oligo2, also termed Class B basic helix-loop-helix protein 1 (bHLHb1), or Class E basic helix-loop-helix protein 19 (bHLHe19), or protein kinase C-binding protein 2, or protein kinase C-binding protein RACK17, is required for oligodendrocyte and motor neuron specification in the spinal cord, as well as for the development of somatic motor neurons in the hindbrain. It cooperates with OLIG1 to establish the MN progenitors (pMN) domain of the embryonic neural tube. Oligo3, also termed Class B basic helix-loop-helix protein 7 (bHLHb7), or Class E basic helix-loop-helix protein 20 (bHLHe20), is expressed in the ventricular zone of the dorsal alar plate of the hindbrain and involved in regulating the development of dorsal and ventral spinal cord. It may determine the distinct specification program of class A neurons in the dorsal part of the spinal cord and suppress specification of class B neurons.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 18859021  59 LRLK-NPSERRqnasekeklRMRDLTKALHHLRSFLPASVAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19725   1 LRLKiNSRERK---------RMHDLNSALDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTNSL 58

basic helix-loop-helix (bHLH) domain found in helix-loop-helix protein 2 (HEN-2) and similar proteins; HEN-2, also termed nescient helix-loop-helix 2 (Nhlh2), or Class A basic helix-loop-helix protein 34 (bHLHa34), or nescient helix loop helix 2 (NSCL-2), is a neuron-specific bHLH transcription factor that may serve as DNA-binding protein and may be involved in the control of cell-type determination, possibly within the developing nervous system.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18859021  52 IMRKKRRLRLKNPSERRQNASEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19702   1 LSREEKRRRRRATAKYRSAHATRERIRVEAFNLAFAELRKLLPT--LPPDKKLSKIEILRLAICYISYLNHVL 71

basic helix-loop-helix (bHLH) domain found in Fer3-like protein (FERD3L) and similar proteins; FERD3L, also termed basic helix-loop-helix protein N-twist, or Class A basic helix-loop-helix protein 31 (bHLHa31), or nephew of atonal 3 (NATO3), or Neuronal twist (NTWIST), is a bHLH transcription factor expressed in the developing central nervous system (CNS). It regulates floor plate (FP) cells development. FP is a critical organizing center located at the ventral-most midline of the neural tube. FERD3L binds to the E-box and functions as inhibitor of transcription.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859021  58 RLRLKNPSERRQnASEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLS 121
Cdd:cd11415   1 RKRVITYAQRQA-ANIRERRRMFNLNEAFDKLRKKVPT--FAYEKRLSRIETLRLAIVYISFMT 61

basic helix-loop-helix (bHLH) domain found in heart- and neural crest derivatives-expressed protein 2 (HAND2) and similar proteins; HAND2, also termed Class A basic helix-loop-helix protein 26 (bHLHa26), or deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2 (dHAND), is a bHLH transcription factor that is essential for cardiac morphogenesis, particularly for the formation of the right ventricle and of the aortic arch arteries.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLSSQLGLSEE 129
Cdd:cd11471   1 RRGTANRKERRRTQSINSAFAELRECIPN--VPADTKLSKIKTLRLATSYIAYLMDLLAKDDQ 61

basic helix-loop-helix (bHLH) domain found in neurogenic differentiation factor 1 (NeuroD1) and similar proteins; NeuroD1, also termed Class A basic helix-loop-helix protein 3 (bHLHa3), is a neuronal bHLH transcription factor involved in the development and maintenance of the endocrine pancreas and neuronal elements. It acts as an essential regulator of glutamatergic neuronal differentiation. Loss of NeuroD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18859021  54 RKKRRLRLKNPSERRQNASEKEKLRMRDLTKALHHLRSFLPASVAPvgQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19719  15 KKMTKARLERFKMRRMKANARERNRMHGLNAALDNLRKVVPCYSKT--QKLSKIETLRLAKNYIWALSEIL 83

basic helix-loop-helix (bHLH) domain found in protein atonal homologs ATOH1, ATOH7 and similar proteins; The family includes ATOH1 and ATOH7. ATOH1, also termed Class A basic helix-loop-helix protein 14 (bHLHa14), or helix-loop-helix protein hATH-1 (hATH1), or Math1, or Cath1, is a proneural bHLH transcription factor that is essential for inner ear hair cell differentiation. It dimerizes with E47 and activates E-box (CANNTG) dependent transcription. ATOH1 is a mammalian homolog of the Drosophila melanogaster gene atonal and mouse atonal homolog 1 (Math1). ATOH7, also termed Class A basic helix-loop-helix protein 13 (bHLHa13), or helix-loop-helix protein hATH-5 (hATH5), or Math5, is a bHLH transcription factor involved in the differentiation of retinal ganglion cells. The family also includes protein Amos (also termed absent MD neurons and olfactory sensilla protein, or reduced olfactory organs protein, or rough eye protein). It is a bHLH transcription factor that promotes multiple dendritic neuron formation in the Drosophila peripheral nervous system.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASVApvGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd11430   1 RRLAANARERRRMNGLNRAFDQLRSVVPSIGN--DKKLSKYETLQMAQIYIETLSELL 56

basic helix-loop-helix (bHLH) domain found in muscle, intestine and stomach expression 1 (MIST-1) family; MIST-1, also termed Class A basic helix-loop-helix protein 15 (bHLHa15), or Class B basic helix-loop-helix protein 8 (bHLHb8), is a bHLH transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. It is essential for cytoskeletal organization and secretory activity. It also functions as a potent endoplasmic reticulum (ER) stress-inducible transcriptional regulator. MIST-1 is capable of binding to E-box (CANNTG) motifs as a homodimer or a heterodimer with E-proteins (E12 and E47) to regulate transcription. The family also includes Drosophila melanogaster protein dimmed and similar proteins. Dimmed, also termed DIMM, is a bHLH transcription factor that regulates neurosecretory (NS) cell function and neuroendocrine cell fate in Drosophila.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASVApvGQTLTKIETLRLTIQYISFLSS 122
Cdd:cd11426   1 RRLESNERERLRMHQLNDAFQALREVIPHVRS--ERKLSKIETLTLAKNYIKSLTN 54

basic helix-loop-helix (bHLH) domain found in musculin and similar proteins; Musculin, also termed activated B-cell factor 1 (ABF-1), or Class A basic helix-loop-helix protein 22 (bHLHa22), is a bHLH transcription factor expressed in activated B lymphocytes. It acts as a transcription repressor capable of inhibiting the transactivation capability of TCF3/E47. Musculin may play a role in regulating antigen-dependent B-cell differentiation. The mouse homolog, musculin, is suggested to be a repressor of myogenesis that is expressed in developing muscle and in the spleen. Musculin heterodimerizes with products of the E2A gene.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPAsvAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19703   4 QRNAANARERARMRVLSKAFSRLKTSLPW--VPPDTKLSKLDTLRLASSYIAHLRQLL 59

basic helix-loop-helix (bHLH) domain found in T-cell acute lymphocytic leukemia protein 1 (TAL-1) and similar proteins; TAL-1, also termed Class A basic helix-loop-helix protein 17 (bHLHa17), or stem cell protein (SCL), or T-cell leukemia/lymphoma protein 5, is a hematopoietic-specific bHLH transcription factor that functions in embryonic and adult hematopoiesis in vertebrates. It is also required for embryonic vascular remodeling. It acts as a regulator of erythroid differentiation and binds to regulatory regions of a large cohort of erythroid genes as part of a complex with GATA-1, LMO2 and Ldb1. TAL-1 has been implicated in T-cell acute lymphoblastic leukemia. In common with other tissue-specific bHLH proteins, Tal heterodimerizes with ubiquitously-expressed members of the E2A family and form a DNA-binding complex with an E-box (CANNTG) to regulate transcription at its recognition site.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASvaPVGQTLTKIETLRLTIQYISFLSSQLGLSEEE 130
Cdd:cd19706   4 RRIFTNSRERWRQQNVNGAFAELRKLIPTH--PPDKKLSKNEILRLAMKYINFLAKLLNDQEEE 65

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 5 (ASCL-5) and similar proteins; ASCL-5, also termed Class A basic helix-loop-helix protein 47 (bHLHa47), or achaete-scute homolog 5 (ASH-5), is an uncharacterized bHLH transcription factor that belongs to AS-C (achaete, scute, lethal of scute, and asense) family.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 18859021  69 QNASEKEKLRMRDLTKALHHLRSFLPASVAPvgQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19747   8 QKRNERERQRVKCVNEGYARLRDHLPGAMAE--KRLSKVETLRAAIRYIKYLQDLL 61

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 4 (ASCL-4) and similar proteins; ASCL-4, also termed Class A basic helix-loop-helix protein 44 (bHLHa44), or achaete-scute homolog 4 (ASH-4), or Hash4, is a bHLH transcriptional regulator that may be involved in skin development.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18859021  67 RRQNasEKEKLRMRDLTKALHHLRSFLPASVAPvgQTLTKIETLRLTIQYISFLSSQLG 125
Cdd:cd19746  10 RKRN--ERERQRVRCVNEGYARLREHLPQELAD--KRLSKVETLRAAIDYIKHLQELLE 64

basic helix-loop-helix (bHLH) domain found in protein lyl-1 and similar proteins; Lyl-1, also termed Class A basic helix-loop-helix protein 18 (bHLHa18), or lymphoblastic leukemia-derived sequence 1, is a proto-oncogenic bHLH transcription factor involved in T-cell acute lymphoblastic leukemia. It plays an important role in hematopoietic stem cell function and is required for the late stages of postnatal angiogenesis to limit the formation of new blood vessels, notably by regulating the activity of the small GTPase Rap1. LYL-1 deficiency induces a stress erythropoiesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASvaPVGQTLTKIETLRLTIQYISFLSSQLG 125
Cdd:cd19705   6 RRVFTNSRERWRQQNVNGAFAELRKLIPTH--PPDKKLSKNEILRLAMKYIDFLVTLLR 62

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factor 3 (Oligo3) and similar proteins; Oligo3, also termed Class B basic helix-loop-helix protein 7 (bHLHb7), or Class E basic helix-loop-helix protein 20 (bHLHe20), is a bHLH transcription factor that is expressed in the ventricular zone of the dorsal alar plate of the hindbrain and involved in regulating the development of dorsal and ventral spinal cord. It may determine the distinct specification program of class A neurons in the dorsal part of the spinal cord and suppress specification of class B neurons.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 18859021  56 KRRLRLKNPSERRQNASEKEKLRMRDLTKALHHLRSFLPASVAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd18941   5 KKQLSEQDLQQLRLKINGRERKRMHDLNLAMDGLREVMPYAHGPSVRKLSKIATLLLARNYILMLTSSL 73

basic helix-loop-helix (bHLH) domain found in oligodendrocyte transcription factor 1 (Oligo1) and similar proteins; Oligo1, also termed Class B basic helix-loop-helix protein 6 (bHLHb6), or Class E basic helix-loop-helix protein 21 (bHLHe21), is a bHLH transcription factor that promotes formation and maturation of oligodendrocytes, especially within the brain.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859021  66 ERRQNASEKEKLRMRDLTKALHHLRS-FLPASVAPV----GQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd18942   5 QLRRKINSRERKRMQDLNLAMDALREvILPYSAAHCqsspGRKLSKIATLLLARNYILLLGSSL 68

basic helix-loop-helix (bHLH) domain found in Class E basic helix-loop-helix protein 23 (bHLHe23) and similar proteins; bHLHe23, also termed Class B basic helix-loop-helix protein 4 (bHLHb4), is an OLIG-related bHLH transcription factor that is expressed in rod bipolar cells and is required for rod bipolar cell maturation. bHLHe23 have roles in spinal interneuron differentiation by mechanisms linked to the Notch signaling pathway. It modulates the expression of genes required for the differentiation and/or maintenance of pancreatic and neuronal cell types.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 18859021  54 RKKRRLRLK-NPSERRqnasekeklRMRDLTKALHHLRSFLPASVAPVGQTLTKIETLRLTIQYI 117
Cdd:cd18953   2 KEQRSLRLSiNARERR---------RMHDLNDALDGLRSVIPYAHSPSVRKLSKIATLLLAKNYI 57

basic helix-loop-helix (bHLH) domain found in achaete-scute complex-like (ASCL) family; The achaete-scute complex-like (ASCL, also known as achaete-scute complex homolog or ASH) family of bHLH transcription factors, ASCL1-5, have been implicated in cell fate specification and differentiation. They are critical for proper development of the nervous system. The deregulation of ASCL plays a key role in psychiatric and neurological disorders. ASCL-1, also termed Class A basic helix-loop-helix protein 46 (bHLHa46), or achaete-scute homolog 1 (ASH-1), or mammalian achaete-scute homolog 1 (Mash1), is a neural-specific bHLH transcription factor that is expressed in subsets of neural progenitors in both the central and peripheral nervous system. It plays a key role in neuronal differentiation and specification in the nervous system. ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete-scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves. ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis. The family also includes Drosophila melanogaster achaete-scute complex (AS-C) proteins, which consists of lethal of scute (also known as achaete-scute complex protein T3 or AST3), scute (also known as achaete-scute complex protein T4 or AST4), achaete (also known as achaete-scute complex protein T5 or AST5), and asense (also known as achaete-scute complex protein T8 or AST8). They are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system, as well as in sex determination and dosage compensation.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18859021  66 ERRqnaSEKEKLRMRDLTKALHHLRSFLPasVAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd11418   3 ARR---NERERRRVQAVNDAFDRLRQHVP--YLKRRKKLSKVKTLRRAIEYIRHLQKLL 56

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster helix loop helix protein 3B (dHLH3B) and similar proteins; Drosophila HLH3B is an uncharacterized bHLH transcription factor that belongs to the T-cell acute lymphocytic leukemia protein/ lymphoblastic leukemia-derived sequence (TAL/LYL) family.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASvaPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19708   1 RRMFTNSRERWRQQNVNGAFAELRKLVPTH--PPDKKLSKNEILRLAIKYIRLLSNVL 56

basic helix-loop-helix (bHLH) domain found in protein atonal homolog 8 (ATOH8) and similar proteins; ATOH8, also termed Class A basic helix-loop-helix protein 21 (bHLHa21), or helix-loop-helix protein hATH-6 (hATH6), is a bHLH shear-stress-responsive transcription factor expressed in activated satellite cells and proliferating myoblasts of human skeletal muscle tissue. It regulates endothelial cell proliferation, migration and tube-like structures formation. ATOH8 binds a palindromic (canonical) core consensus DNA sequence 5'-CANNTG- 3' known as an E-box element, possibly as a heterodimer with other bHLH proteins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 18859021  66 ERRQNASEKEKLRMRDLTKALHHLRSFLPASvaPVGQTLTKIETLRLTIQYISFLSSQLGLSEE 129
Cdd:cd11421   7 QRRIEANARERTRVHTISAAFEALRKAVPSY--SYNQKLSKLAILRIACSYILALARLADLDYS 68

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 2 (ASCL-2) and similar proteins; ASCL-2, also termed achaete-scute homolog 2 (ASH-2), or Class A basic helix-loop-helix protein 45 (bHLHa45), or mammalian achaete scute homolog 2 (Mash2), is a bHLH transcription factor that is involved in Schwann cell differentiation and control of proliferation in adult peripheral nerves.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 18859021  64 PSERRqnaSEKEKLRMRDLTKALHHLRSFLPASVApvGQTLTKIETLRLTIQYISFLSSQLG 125
Cdd:cd19743   3 AVERR---NERERNRVKLVNLGFAALRQHVPQGGA--SKKMSKVETLRSAVEYIRALQRLLG 59

basic helix-loop-helix (bHLH) domain found in achaete-scute-like protein 3 (ASCL-3) and similar proteins; ASCL-3, also termed Class A basic helix-loop-helix protein 42 (bHLHa42), or bHLH transcriptional regulator Sgn-1, or achaete-scute homolog 3 (ASH-3), is a bHLH transcription factor specifically localized in the duct cells of the salivary glands. It may act as transcriptional repressor that inhibits myogenesis.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18859021  67 RRQNasEKEKLRMRDLTKALHHLRSFLPASVAPvgQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19745   6 RKRN--ERERQRVKCVNEGYAKLRRHLPQEYSE--KRLSKVETLRAAIKYIKHLQSVL 59

basic helix-loop-helix (bHLH) domain found in twist-related protein (TWIST) family; The TWIST family includes TWIST1 and TWIST2, which are highly homologous bHLH transcription factors that promote epithelial-mesenchymal transition (EMT) during development and tumor metastasis. They are involved in the negative regulation of cellular determination and in the differentiation of several lineages, including myogenesis, osteogenesis, and neurogenesis. TWIST factors express in broad partially-overlapping patterns during embryo development and dimerize with a broad sets of dimer partners that form numerous unique transcriptional complexes to regulate embryonic development.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 18859021  67 RRQNASEKEKLRMRDLTKALHHLRSFLPASVApvgQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd11464   1 QRVLANVRERQRTQSLNEAFTSLRKIIPTLPS---DKLSKIQTLKLAARYIDFLYQVL 55

basic helix-loop-helix (bHLH) domain found in Drosophila melanogaster myogenic-determination protein (dMYOD) and similar proteins; dMYOD, also termed protein nautilus, or Myd, may play an important role in the early development of muscle in Drosophila.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 18859021  66 ERRQNASEKEKLRMRDLTKALHHLRSflpASVAPVGQTLTKIETLRLTIQYISFLSSQL 124
Cdd:cd19699   1 DRRKAATMRERRRLRKVNEAFEVLKR---RTCPNPNQRLPKVEILRNAIEYIESLEDLL 56

basic helix-loop-helix (bHLH) domain found in muscle-specific regulatory factor 4 (MRF4) and similar proteins; MRF4, also termed Class C basic helix-loop-helix protein 4 (bHLHc4), or myogenic factor 6 (Myf-6), is a bHLH transcription factor associated with myogenesis. It plays a role in skeletal muscle differentiation.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 18859021  66 ERRQNASEKEKLRMRDLTKALHHLRSflpASVAPVGQTLTKIETLRLTIQYISFLSSQL-GLSEEE 130
Cdd:cd18934   1 DRRKAATLRERRRLKKINEAFEALKR---RTVPNPNQRLPKVEILRSAINYIEKLQDLLhSLDQQE 63